Effect of adenovirus-mediated gene transfer of Olig1 on oligodendrocyte differentiation and remyelination in a rat model of focal cerebral ischemia

BACKGROUND:The transcription factor Olig1 is required for oligodendrocyte maturation and demyelinated lesion repair,and is a key regulator of myelinogenesis following ischemia. OBJECTIVE:To examine the efficacy of intraventricular injection of a recombinant adenovirus-expressing Olig1 gene(Ad5-Olig1-eGFP) on oligodendrocyte maturation and myelin repair following focal cerebral ischemia. DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Department of Neurology,Beijing Friendship Hospital Affiliated to Capital Medical University from January 2007 to March 2008. MATERIALS:Adenovirus and a recombinant adenovirus containing Olig1 gene(Ad5-Olig1) were provided by Vector Gene Technology,China. METHODS:All 50 rats were induced by middle cerebral artery occlusion.A total of 46 rats were successfully induced and were subsequently randomly assigned to a adenovirus(Ad5) group and a recombinant adenovirus-expression Olig1 gene(Ad5-Olig1) group,with 23 rats per group.One day after middle cerebral artery occlusion,either Ad5-Olig1-eGFP or Ad5-eGFP(10μL,2.3×1011/mL) was injected into the lateral ventricle on the ischemic hemisphere. MAIN OUTCOME MEASURES:Adenovirus-mediated Olig1 gene expression in vitro and in vivo was measured by reverse transcription-polymerase chain reaction and immunofluorescence, respectively.Myelin basic protein(MBP) levels were evaluated by Western Blot,immunostaining, and electron microscopy. RESULTS:Exogenous Olig1 expression was measured at the periventricular zone of the lateral ventricle 1 day after Ad5-Olig1 injection.In the Ad5-Olig1-treated group,MBP protein levels and average intensity of MBP-immunoreactivity(-ir) increased 28 days after middle cerebral artery occlusion,compared with the control group(P<0.01,P<0.05).Furthermore,myelinated axonal numbers markedly increased following Ad5-Olig1 treatment. CONCLUSION:The present data suggested that Ad5-Olig1 gene therapy increased MBP expression and the number of remyelinating axons following cerebral ischemia.